Maternal vitamin B12 in mice positively regulates bone, but not muscle mass and strength in post-weaning and mature offspring

Am J Physiol Regul Integr Comp Physiol. 2021 Jun 1;320(6):R984-R993. doi: 10.1152/ajpregu.00355.2020. Epub 2021 Mar 24.


Vitamin B12 deficiency has been shown to affect bone mass in rodents and negatively impact bone formation in humans. In this study using mouse models, we define the effect of B12 supplementation in the wild-type mother and B12 deficiency in a mouse genetic model (Gif-/- mice) during gestation on bone and muscle architecture and mechanical properties in the offspring. Analysis of bones from 4-wk-old offspring of the wild-type mother following vehicle or B12 supplementation during gestation (from embryonic day 0.5 to 20.5) showed an increase in bone mass caused by an isolated increase in bone formation in the B12-supplemented group compared with vehicle controls. Analysis of the effect of B12 deficiency in the mother in a mouse genetic model (Gif-/- mice) on the long bone architecture of the offspring showed a compromised cortical and trabecular bone mass, which was completely prevented by a single injection of B12 in the B12-deficient Gif-/- mothers. Biomechanical analysis of long bones of the offspring born from B12-supplemented wild-type mothers showed an increase in bone strength, and conversely, offspring born from B12-deficient Gif-/- mothers revealed a compromised bone strength, which could be rescued by a single injection of B12 in the B12-deficient Gif-/- mother. Muscle structure and function analysis however revealed no significant effect on muscle mass, structure, and grip strength of B12 deficiency or supplementation in Gif-/- mice compared with littermate controls. Together, these results demonstrate the beneficial effect of maternally derived B12 in the regulation of bone structure and function in the offspring.

Keywords: bone; gut; muscle; osteoblasts; vitamin B12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Density / physiology
  • Bone and Bones / metabolism*
  • Dietary Supplements
  • Female
  • Maternal Nutritional Physiological Phenomena / physiology*
  • Mice
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Vitamin B 12 / metabolism*
  • Vitamins / metabolism
  • Weaning


  • Vitamins
  • Vitamin B 12